Reproductive function and behavior are principally controlled via the synthesis and secretion of the neuropeptide, luteinizing hormone releasing hormone (LHRH). In humans an altered emotional state (anorexia nervosa) or hormonal malfunction (hyperprolactinemic amenorrhea) results in a reproductive disorder probably by affecting this parameter. The studies in this application are designed to identify the specific neural and peripheral modulators of LHRH biosynthesis and secretion and the cellular mechanism of its biosynthesis. Techniques have been established to quantitate the hypothalamic content and turnover of the peptide, LHRH, and the neurotransmitters involved in its control (norpinephrine, dopamine, and the brain opiate peptides - the enkephalins). LHRH and enkephalin content will be measured by radioimmunoassay while turnover will be monitored by incorporation of labeled amino acids, purification by reverse phase chromatography and followed by specific immunoprecipitation. Catecholamine content will be quantitated by electrochemical detection (LCEC) and a simultaneous index of turnover will be accomplished by the incorporation of tritiated tyrosine into specific biogenic amines. Experimental models will include studies using an in vitro incubation of rat medial basal hypothalami and an in vivo model where precursors and drugs are administered into the lateral ventricles of the brain. Castrated and hyperprolactinemic (by pituitary transplants) rats will be specifically studied. Pharmacological manipulations will focus on a possible presynaptic inhibition of transmitter and LHRH release using specific alpha 2-receptor agonists and antagonists.